Evaluation of substance P as a neurotransmitter in equine jejunum

Objective-To determine whether substance P (SP) functions as a neurotransmi tter in equine jejunum. Sample Population-Samples of jejunum obtained from horses that did not have lesions in the gastrointestinal tract. Procedure-Jejunal smooth muscle strips, oriented in the plane of the circul ar or longitudinal muscle, were suspended isometrically in muscle baths. Ne urotransmitter release was induced by electrical field stimulation (EFS) de livered at 2 intensities (30 and 70 V) and various frequencies on muscle st rips that were maintained at low tension or were under contraction. A neuro kinin-l receptor blocker (CP-96,345) was added to baths prior to EFS to int errupt SP neurotransmission. Additionally, direct effects of SP on muscle s trips were evaluated, and SP-like immunoreactivity was localized in intesti nal tissues, using indirect immunofluorescence testing. Results-Substance P contracted circularly and longitudinally oriented muscl e strips. Prior treatment with CP-96,345 altered muscle responses to SP and EFS, suggesting that SP was released from depolarized myenteric neurons. D epending on orientation of muscle strips and stimulation variables used, CP -96,345 increased or decreased the contractile response to EFS. Substance P -like immunoreactivity was detect ed in the myenteric plexus and circular m uscle layers. Conclusions and Clinical Relevance-Substance P appears to function as a neu rotransmitter in equine jejunum. It apparently modulates smooth muscle cont ractility, depending on preexisting conditions. Effects of SP may be altere d in some forms of intestinal dysfunction. Altering SP neurotransmission in the jejunum may provide a therapeutic option for motility disorders of hor ses that are unresponsive to adrenergic and cholinergic drugs.